Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Abstract

Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n539). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS. Asian Journal of Andrology (2013) Keywords: denervation; nerve growth factor; prostate growth; ventral prostate INTRODUCTION Benign prostatic hyperplasia (BPH) is a serious health concern worldwide and is an underlying cause of many lower urinary tract symptoms (LUTS). LUTS is common in aging men and a population based survey performed in five countries reports that ,64% of adults experience at least one LUTS symptom.1 LUTS has a profound impact on social functioning and quality of life in affected men 2,3 with similar effects reported as after a heart attack or stroke.4 BPH can induce acute urinary retention, incontinence, recurrent urinary tract infection or obstructive uropathy. LUTS secondary to BPH generally consists of three components: benign proliferation of the stroma and epithelium, bladder outlet obstruction and symptoms resulting from obstruction.

A study of prostate volumes in patients with spinal cord injury

“…In rats, unilateral sympathectomy leads to ipsilateral atrophy of the prostate with decrease in weight, DNA and protein content . This is accompanied by an increase in nerve growth factor (NGF) levels in the ventral prostate …”

“…14 This is accompanied by an increase in nerve growth factor (NGF) levels in the ventral prostate. 15 The neuroanatomy of the sympathetic system in humans is complex. Its first neuron arises in the hypothalamus.…”